CELL SIGNALING LEADING TO UV-INDUCED CELL INJURY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 AMP激活的蛋白激酶或AMPK是一种进化上保守的细胞能量状态感受器，在耗尽ATP的各种细胞压力下被激活。然而，AMPK在紫外线和过氧化氢诱导的氧化应激导致皮肤老化或皮肤癌中的可能参与还没有完全的研究。 SIRT1是一个高度保守的基因家族(Sirtuins)的成员，该基因编码依赖NAD+的脱乙酰基酶，最初被发现能使组蛋白去乙酰化，从而提高DNA的稳定性，延长酵母和高等生物(包括哺乳动物)的生存时间。已发现SIRT1作为一种脱乙酰酶参与多种细胞通路，包括应激反应、细胞凋亡和轴突变性。 然而，SIRT1在UV信号通路中的作用仍不清楚。在这一资助期间，我们研究了AMPK和SIRT1在紫外线诱导培养的皮肤角质形成细胞凋亡中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. AMP-activated protein kinase or AMPK is an evolutionarily conserved sensor of cellular energy status, activated by a variety of cellular stresses that deplete ATP. However, the possible involvement of AMPK in UV- and H2O2-induced oxidative stresses that lead to skin aging or skin cancer has not been fully studied. SIRT1 is a member of a highly conserved gene family (sirtuins) encoding NAD+-dependent deacetylases, originally found to deacetylate histones leading to increased DNA stability and prolonged survival in yeast and higher organisms, including mammals. SIRT1 has been found to function as a deacetylase for numerous protein targets involved in various cellular pathways, including stress responses, apoptosis, and axonal degeneration. However, the role of SIRT1 in UV signaling pathways remains unknown. In this funding period, we investigated the roles of AMPK and SIRT1 in UV-induced cellular apoptosis in cultured skin keratinocytes.